具有靛红结构的吡唑衍生物的合成及其诱导非小细胞肺癌A549细胞凋亡的研究
发布时间：2018-10-05 10:32
【摘要】：基于药效团拼合的设计原理,以4-羟基苯乙酮为原料,通过加成、环化、取代、肼解和缩合等多步反应构建了两类含有靛红结构的吡唑衍生物,共计12个目标产物,其结构经~~1H NMR,~(13)C NMR和HRMS确证.采用细胞计数试剂盒-8(CCK-8)法测试目标产物对人非小细胞肺癌细胞A549的体外抑制作用,部分化合物显示出一定的抗增殖活性,其中N'-(3-亚氨基-6-氯吲哚-2-酮)-1-苯甲基-3-(4-甲氧基苯基)-1H-吡唑-5-甲酰肼(7e)和N'-(3-亚氨基-6-溴吲哚-2-酮)-1-苯甲基-3-(4-甲氧基苯基)-1H-吡唑-5-甲酰肼(7f)的IC_(50)值分别为30.41和29.69μmol/L.流式细胞术检测表明,化合物7f能够剂量依赖性地诱导A549细胞凋亡,并降低线粒体膜电位,但对细胞周期没有影响.上述研究证明,目标产物7f能够通过线粒体途径诱导A549细胞凋亡,从而发挥抗肿瘤活性.
[Abstract]:Based on the design principle of pharmacophore assembly, two kinds of pyrazole derivatives with indirubin structure were synthesized from 4-hydroxyacetophenone by multi-step reactions such as addition, cyclization, substitution, hydrazine hydrolysis and condensation. Its structure was confirmed by 1H NMR,~ (13) C NMR and HRMS). The inhibitory effect of the target product on human non-small cell lung cancer cell line A549 in vitro was tested by cell count kit 8 (CCK-8). Some of the compounds showed certain antiproliferative activity. The IC_ (50) values of N- (3-Imino-6-chlorindole-2-one) -1-phenyl-methyl-3- (4-methoxyphenyl) -1H-pyrazolyl hydrazide (7e) and N- (3-imino-6-bromoindole -2-one) -1-phenylmethyl-3- (4-methoxyphenyl) -1H-pyrazole-5-formyl hydrazide (7f) were 30.41 渭 mol/L. and 29.69 渭 mol/L., respectively. Flow cytometry showed that compound 7f could induce apoptosis of A549 cells in a dose-dependent manner and decrease mitochondrial membrane potential, but had no effect on cell cycle. These results suggest that target product 7f can induce apoptosis of A549 cells through mitochondrial pathway, thus exerting antitumor activity.
【作者单位】： 遵义医学院药学院;成都大学四川抗菌素工业研究所;
【基金】：贵州省科技厅(Nos.[2014]7565,[2014]7557,[2015]6010) 遵义医学院博士科研启动基金(No.F-631);遵义医学院大学生创新创业(Nos.[2014]5811,[2014]2918);遵义医学院学科建设(药物化学)资助项目 国家级大学生创新创业(No.201510661009)~~
【分类号】：O626;TQ460.1
本文编号：2253048
[Abstract]:Based on the design principle of pharmacophore assembly, two kinds of pyrazole derivatives with indirubin structure were synthesized from 4-hydroxyacetophenone by multi-step reactions such as addition, cyclization, substitution, hydrazine hydrolysis and condensation. Its structure was confirmed by 1H NMR,~ (13) C NMR and HRMS). The inhibitory effect of the target product on human non-small cell lung cancer cell line A549 in vitro was tested by cell count kit 8 (CCK-8). Some of the compounds showed certain antiproliferative activity. The IC_ (50) values of N- (3-Imino-6-chlorindole-2-one) -1-phenyl-methyl-3- (4-methoxyphenyl) -1H-pyrazolyl hydrazide (7e) and N- (3-imino-6-bromoindole -2-one) -1-phenylmethyl-3- (4-methoxyphenyl) -1H-pyrazole-5-formyl hydrazide (7f) were 30.41 渭 mol/L. and 29.69 渭 mol/L., respectively. Flow cytometry showed that compound 7f could induce apoptosis of A549 cells in a dose-dependent manner and decrease mitochondrial membrane potential, but had no effect on cell cycle. These results suggest that target product 7f can induce apoptosis of A549 cells through mitochondrial pathway, thus exerting antitumor activity.
【作者单位】： 遵义医学院药学院;成都大学四川抗菌素工业研究所;
【基金】：贵州省科技厅(Nos.[2014]7565,[2014]7557,[2015]6010) 遵义医学院博士科研启动基金(No.F-631);遵义医学院大学生创新创业(Nos.[2014]5811,[2014]2918);遵义医学院学科建设(药物化学)资助项目 国家级大学生创新创业(No.201510661009)~~
【分类号】：O626;TQ460.1
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